Intraoperative hyperthermia in conjunction with multi-schedule chemotherapy (pre-, intra- and post-operative), by-pass surgery, and post-operative radiotherapy for the management of unresectable pancreatic adenocarcinoma

Abstract

The aim of this study was to evaluate the potential role of intraoperative hyperthermia (IOHT) in the management of stage IV pancreatic adenocarcinoma. Twenty-seven patients (group A) received pre-operative chemotherapy (5-FU), by-pass surgery with intraoperative bolus infusion of 5-FU and post-operatively multi-agent chemotherapy plus sandostatin and external beam irradiation (45Gy, 25 fractions, 5 days a week). In a non-randomized way, 10 patients (group B) received an additional single session of IOHT (43-45 degrees C, 1h) performed directly on the tumour using a waveguide applicator (433MHz) with interstitial measurements of temperature measured. A brief instrument was developed for evaluating patients' quality of life. No progressive disease (PD) was noticed in group B vs 11% (3/27) of PD in group A. There was also a significant increase of overall survival (OS) in group B vs A patients (p = 0.029, log-rank test). Moreover, there was a significant improvement for group B vs A patients regarding Karnofsky performance status (p < 0.001, Mann-Whitney test), pain score (p < 0.001, Mann-Whitney test) and quality of life score (p = 0.031, Mann-Whitney test). A significant correlation was noticed between OS and thermal parameters such as average T(min) (p = 0.043), average T(max) (p = 0.027) and cumulative minutes T(90) >or= 44 degrees C (p < 0.001). Combined IOHT with chemotherapy (pre-, intra- and post-operative) and external beam post-operative radiotherapy seem to have a potential benefit in the management of unresectable adenocarcinoma of the pancreas, concerning local response, OS and quality of life. Further clinical studies to evaluate the benefit of IOHT suggested in this study are warranted.

The clinical benefit of hyperthermia in pancreatic cancer: a systematic review

“…To investigate efficacy of hyperthermia as adjuvant therapy in pancreatic cancer patients, we analysed response rate, [68] describes same study as included study [57]. b cohort in [67] largely overlaps with cohort in included study [54].…”

“…After the first and second selection (Figure 1), 14 studies were included [53][54][55][56][57][58][59][60][61][62][63][64][65][66]. Two patient cohorts were each described in two articles; for these we excluded the oldest [67,68] and included the latest [54,57].…”

“…Two patient cohorts were each described in two articles; for these we excluded the oldest [67,68] and included the latest [54,57]. Based on the reported patient characteristics in [56], it was evident there was no overlap of this patient cohort with the cohort in references [57,68]. One included article was written in German [58]; all others were written in English.…”

“…The included 14 studies combined 395 pancreatic cancer patients of whom 248 received HT (Table 1). Six out of 14 studies used a control population that enabled a comparison between treatments with and without hyperthermia [54,55,57,60,62,66]. In two studies, patients with a variety of carcinomas were included, but data were reported for the pancreatic patients separately [53,59].…”

Review: The Role of Hyperthermia in Treating Pancreatic Tumors

“…Criticism 20 years ago was regarding the apparent inability to sufficiently generate surface heat [5]. A Greek group published promising data about unresectable palliative cases with a scheme of multi-schedule chemotherapy combined with radiation (45 Gy) plus a single session of hyperthermia during bypass surgery [6]. Hyperthermia was applied at 433 Mhz frequency which is basically suitable to efficiently heat the surface area.…”